INTRODUCTION: High resolution functional magnetic resonance imaging (fMRI) of the rat cortex provides a valuable technique for investigating plasticity and functional recovery following trauma. fMRI has been used to demonstrate cortical activation in anaesthetized animals by exploiting the BOLD effect and the signal intensity changes typically seen are in the order of a few percent. METHODS: Six male rats were anesthetized with halothane in oxygen for venous and arterial catheterization then switched to a-chloralose for the remainder of the experiment and images were obtained on a 4.7T Varian INOVA system. Gradient echo (GRE) images were acquired every 6 seconds. For comparison high speed T2-weighted spin echo (SE) fMRI was performed using a RARE sequence. To increase the sensitivity to microscopic magnetic susceptibility variations, the first echo time was increased to 56ms. The fMRI activation paradigm consisted of off-on-off sequence with each period lasting 60s. Forepaw stimulation was performed with a train of 3V pulses of 3ms duration at 3Hz, delivered via a pair of small needle electrodes inserted subcutaneously in the left paw. Experiments were performed with both the GRE and RARE sequences before and after injection of Combidex*. RESULTS: A 4-5% increase in signal intensity was seen with the GRE imaging (BOLD effect) during activation. Following injection of Combidex*, there was a dramatic 15-20% decrease in signal intensity during activation reflecting a change in CBV. Using these optimal conditions higher resolution 128x128 pixel GRE images with in plane resolution of greater 250mm could be readily obtained. The signal change measured with the RARE sequence during activation was comparable to that seen with the GRE sequence using the BOLD mechanism. However, after injection of contrast agent 4-5% reduction in activation signal change was detected. CONCLUSIONS: High resolution functional maps of the rat cortex following sensory stimulation can be readily obtained using GRE sequences or fast SE sequences in conjunction with Combidex*. Tailored MR protocols can be made selective for different vascular components of the activation response. This approach is relatively insensitive to macroscopic susceptibility and is thus ideally suited to high fields fMRI experiments in animals.